Scenarios for the long-term efficacy of amyloid-targeting therapies in the context of the natural history of Alzheimer's disease
Raket, Lars Lau LU
; Cummings, Jeffrey
; Moscoso, Alexis
; Villain, Nicolas
and Schöll, Michael
LU
(2024)
In Alzheimer's and Dementia
20(9).
p.6374-6383
- Abstract
INTRODUCTION: Recent clinical trials of amyloid beta (Aβ)-targeting therapies in Alzheimer's disease (AD) have demonstrated a clinical benefit over 18 months, but their long-term impact on disease trajectory is not yet understood. We propose a framework for evaluating realistic long-term scenarios. METHODS: Results from recent phase 3 trials of Aβ-targeting antibodies were integrated with an estimate of the long-term patient-level natural history trajectory of the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score to explore realistic long-term efficacy scenarios. RESULTS: Three distinct long-term efficacy scenarios were examined, ranging from conservative to optimistic. These extrapolations of positive phase 3 trials suggested... (More)
INTRODUCTION: Recent clinical trials of amyloid beta (Aβ)-targeting therapies in Alzheimer's disease (AD) have demonstrated a clinical benefit over 18 months, but their long-term impact on disease trajectory is not yet understood. We propose a framework for evaluating realistic long-term scenarios. METHODS: Results from recent phase 3 trials of Aβ-targeting antibodies were integrated with an estimate of the long-term patient-level natural history trajectory of the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score to explore realistic long-term efficacy scenarios. RESULTS: Three distinct long-term efficacy scenarios were examined, ranging from conservative to optimistic. These extrapolations of positive phase 3 trials suggested treatments delayed onset of severe dementia by 0.3 to 0.6 years (conservative), 1.1 to 1.9 years (intermediate), and 2.0 to 4.2 years (optimistic). DISCUSSION: Our study provides a common language for long-term impact of disease-modifying treatments. Our work calls for studies with longer follow-up and results from early intervention trials to provide a comprehensive assessment of these therapies' true long-term impact. Highlights: We present long-term scenarios of the efficacy of AD therapies. In this framework, scenarios are defined relative to the natural history of AD. Long-term projections with different levels of optimism can be compared. It provides a common language for expressing beliefs about long-term efficacy.
(Less)
- author
- Raket, Lars Lau
LU
; Cummings, Jeffrey
; Moscoso, Alexis
; Villain, Nicolas
and Schöll, Michael
LU
- organization
- publishing date
- 2024-09
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- amyloid-targeting therapies, clinical trials, disease modeling, disease modification, long-term efficacy, time saving
- in
- Alzheimer's and Dementia
- volume
- 20
- issue
- 9
- pages
- 10 pages
- publisher
- Wiley
- external identifiers
-
- scopus:85200007935
- pmid:39073291
- ISSN
- 1552-5260
- DOI
- 10.1002/alz.14134
- language
- English
- LU publication?
- yes
- id
- 2aa66eca-3531-4c06-a1a7-6c02110a3c74
- date added to LUP
- 2024-11-11 15:51:35
- date last changed
- 2025-07-08 11:25:42
@article{2aa66eca-3531-4c06-a1a7-6c02110a3c74,
abstract = {{<p>INTRODUCTION: Recent clinical trials of amyloid beta (Aβ)-targeting therapies in Alzheimer's disease (AD) have demonstrated a clinical benefit over 18 months, but their long-term impact on disease trajectory is not yet understood. We propose a framework for evaluating realistic long-term scenarios. METHODS: Results from recent phase 3 trials of Aβ-targeting antibodies were integrated with an estimate of the long-term patient-level natural history trajectory of the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score to explore realistic long-term efficacy scenarios. RESULTS: Three distinct long-term efficacy scenarios were examined, ranging from conservative to optimistic. These extrapolations of positive phase 3 trials suggested treatments delayed onset of severe dementia by 0.3 to 0.6 years (conservative), 1.1 to 1.9 years (intermediate), and 2.0 to 4.2 years (optimistic). DISCUSSION: Our study provides a common language for long-term impact of disease-modifying treatments. Our work calls for studies with longer follow-up and results from early intervention trials to provide a comprehensive assessment of these therapies' true long-term impact. Highlights: We present long-term scenarios of the efficacy of AD therapies. In this framework, scenarios are defined relative to the natural history of AD. Long-term projections with different levels of optimism can be compared. It provides a common language for expressing beliefs about long-term efficacy.</p>}},
author = {{Raket, Lars Lau and Cummings, Jeffrey and Moscoso, Alexis and Villain, Nicolas and Schöll, Michael}},
issn = {{1552-5260}},
keywords = {{amyloid-targeting therapies; clinical trials; disease modeling; disease modification; long-term efficacy; time saving}},
language = {{eng}},
number = {{9}},
pages = {{6374--6383}},
publisher = {{Wiley}},
series = {{Alzheimer's and Dementia}},
title = {{Scenarios for the long-term efficacy of amyloid-targeting therapies in the context of the natural history of Alzheimer's disease}},
url = {{http://dx.doi.org/10.1002/alz.14134}},
doi = {{10.1002/alz.14134}},
volume = {{20}},
year = {{2024}},
}